Regulation of T cell receptor signaling by protein acyltransferase DHHC21

Ying Fan, Bieerkehazhi Shayahati, Ritika Tewari, Darren Boehning, Askar M. Akimzhanov
2020 · doi:10.1101/2020.02.10.942078
preprint OA: closed CC-BY-NC-ND-4.0
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Abstract

ABSTRACT S-acylation – reversible post-translational lipidation of cysteine residues – is emerging as an important regulatory mechanism in T cell signaling. Dynamic S-acylation is critical for protein recruitment into the T cell receptor complex and initiation of the subsequent signaling cascade. However, the enzymatic control of protein S-acylation in T cells remains poorly understood. Here, we report a previously uncharacterized role of DHHC21, a member of the mammalian family of DHHC protein acyltransferases, in regulation of the T cell receptor pathway. We found that loss of DHHC21 prevented S-acylation of key T cell signaling proteins, resulting in disruption of the early signaling events and suppressed expression of T cell activation markers. Furthermore, downregulation of DHHC21 prevented activation and differentiation of naïve T cells into effector subtypes. Together, our study provides the first direct evidence that DHHC protein acyltransferases can play an essential role in regulation of T cell-mediated immunity.

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License: CC-BY-NC-ND-4.0